CN102266342A - Application of riboflavin tetrabutyrate to preparation of anxiolytic medicament - Google Patents
Application of riboflavin tetrabutyrate to preparation of anxiolytic medicament Download PDFInfo
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- CN102266342A CN102266342A CN2011101483674A CN201110148367A CN102266342A CN 102266342 A CN102266342 A CN 102266342A CN 2011101483674 A CN2011101483674 A CN 2011101483674A CN 201110148367 A CN201110148367 A CN 201110148367A CN 102266342 A CN102266342 A CN 102266342A
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Abstract
The invention discloses application of riboflavin tetrabutyrate to the preparation of an anxiolytic medicament. The riboflavin tetrabutyrate has the defects of low toxicity, no tranquilizing and ataxia effects of the conventional anxiolytic medicament, and the like. As a major ingredient of the anxiolytic medicament, the riboflavin tetrabutyrate can be used separately and directly or compounded with other medicaments or prepared into various solid preparations or liquid preparations together with different medicinal auxiliary materials. According to the invention, new application of the riboflavin tetrabutyrate is provided.
Description
Technical field
The present invention relates to medical technical field, exactly is the new purposes of Riboflavin Tetrabutyrate in the preparation anxiolytic drugs.
Background technology:
Anxiety neurosis is a kind of neurosis based on anxiety, comprises two kinds of generalized anxiety disorder and panic disorders.The former is that a kind of panic attack with repeatedly is the neurosis of main idiopathy shape.This outbreak is not limited to any specific situation, has unpredictability.The latter refers to a kind of lacking the on tenterhooks and nervous anxiety neurosis of clear and definite object and particular content, and has significant vegetative nerve symptom, muscular tone and motion uneasy.Patient agonizes because of being difficult to stand and can't free.According to statistics, sickness rate is about 1%～2% in China's urban population, and developed country is nearly 10%, and still shows a rising trend.Along with The development in society and economy, the quickening of rhythm of life, the inducement that anxiety neurosis produces also increases thereupon, and sickness rate is tangible ascendant trend.
At present, the medicine that is mainly used in anxiety neurosis treatment has following several:
1. on behalf of medicine, benzodiazepine diazepam (stabilizing), chlordiazepoxide, lorazepam etc. are arranged.But such medicine easily causes Cognitive function damage, and life-time service can produce drug dependence, produces serious withdrawal symptom during drug withdrawal.
2. 5-HT
1AOn behalf of medicine, receptor stimulating agent buspirone, tandospirone etc. are arranged.This medicine and benzodiazepine are relatively, has suitable angst resistance effect, the hypnosis of no benzodiazepine, the effect of flesh pine, life-time service is not seen dependence and withdrawal symptom, but onset is comparatively slow, and often cause dizziness, headache, feel sick, untoward reaction such as vomiting and gastrointestinal dysfunction, might infringement be arranged to hepatic and renal function.
3. Chang Yong antidepressant drug also can play the effect of treatment anxiety after the long term administration.But in the long-term prescription process, untoward reaction such as structural change, the dependency of body tissue organ be strong can appear all.
Therefore, this area presses for the anxiolytic drugs of a kind of efficient, low toxicity of research and development, few side effects.
Riboflavin Tetrabutyrate (riboflavin, 2', 3', 4', 5'-tetrabutyrate, riboflavin tetrabutyrate) has another name called hibon, vitamin B
2Four butyrates abbreviate RTB as, and molecular formula is C
33H
44N
4O
10It has bentiamine
2Effect, be converted into flavin mononucleotide (FMN) (FMN) and flavin adenine dinucleotide (FAD) (FAD) in vivo, be the important coenzyme of Tissue respiration, participate in carbohydrate and lipid metabolism and some oxidation-reduction processes, and can activate vitamin B
6, tryptophan transfer is changed to nicotinic acid, and may be with to keep erythrocytic integrity relevant.At present, Riboflavin Tetrabutyrate is mainly used in thrombosis, atherosclerotic auxiliary treatment clinically, also can be used for vitamin B
2Shortage, oral ulcer, scrotitis, seborrheic dermatitis etc.In addition, the oil-soluble enriching substance that also can be used for food additive, nutritional supplement and riboflavin.
The application of Riboflavin Tetrabutyrate in preparation anxiety and antidepressant drug yet there are no report.
Summary of the invention
The invention discloses the effect antianxity of Riboflavin Tetrabutyrate.
The structural formula of Riboflavin Tetrabutyrate is as follows:
The new purposes that the purpose of this invention is to provide a kind of Riboflavin Tetrabutyrate as the main component of anxiolytic drugs, is a kind of good effect, and the little anxiety new drug of side effect.With the pharmaceutical preparation that Riboflavin Tetrabutyrate is used to prepare treatment and prevention of anxiety, form pharmaceutical composition or complex with various medicinal ingredients or pharmaceutical carrier.
Medicine of the present invention can directly use separately, also can form compound recipe with other medicines and use, and can also use different pharmaceutic adjuvants, makes multiple solid preparation or liquid preparation.Medicine of the present invention and compositions thereof are used with the form of per weight dose, can oral or other form administration, carry out the one or many use according to the type of route of administration, patient's age, body weight, the disease for the treatment of and the order of severity etc. are different.
Advantage of the present invention is: disclosed Riboflavin Tetrabutyrate and had effect antianxity, for it provides new purposes; And toxicity is little, does not have the shortcoming that conventional antianxiety drugs causes calmness, ataxia, brings out side effect such as epilepsy.
The specific embodiment:
In order to understand the present invention better, below with zoopery and its effect of presentation of results, but the present invention also not only is confined to these embodiment, the scope that these embodiment do not limit the present invention in any way.Those skilled in the art belong to the scope of protection of present invention to various changes or the modification that the present invention did.
Embodiment 1: the mice elevated plus-maze test
1. grouping and administration
Laboratory animal is a SPF level male mice in kunming, and body weight 18-22g raises in 12/12 hour light and shade circulation environment, and 22 ± 2 ° of C of temperature do not limit drinking water to raise three days.Fasting is 12 hours before the experiment, experiment same day with animal be divided at random RTB low (20mg/kg), in (40mg/kg), high (80mg/kg) dosage group, blank group (0.5% carboxymethylcellulose sodium solution), stable group (2mg/kg), buspirone group (5 mg/kg), every group of 15 animals adapt to experimental situation 1h at least in advance.
It is the carrier preparation that the basic, normal, high dosage suspension of RTB, diazepam solution and buspirone solution all adopt 0.5% carboxymethylcellulose sodium solution, and administering mode is for irritating stomach, administration volume 10ml/kg.
2. experimental technique
Overhead cross labyrinth device is made by black steel sheet, comprise mutually perpendicular two open arm (long 30cm, wide 6cm) with two close arm (long 30cm, wide 6cm, high 10cm), close the arm opened upper end; There is the platform area of one 5 * 5cm in labyrinth central authorities.The labyrinth is apart from ground 50cm.
All experiments are all carried out in 9:00am to 3:00pm.All laboratory animals 60min after administration carries out behavioristics's test.(60cm * 40cm * 40cm) middle movable lets alone freely to probe into 5min, places the central platform place in overhead cross labyrinth then rapidly, and head is towards opening arm earlier mice to be placed on plastic box before the test.Observe the active situation of mice in 5 minutes.The result with mice enter out the arm number of times percentage ratio (percent open arm entry, OE%) and opening the holdup time percentage ratio of arm (percent closed arm time, OT%) expression.After the test of every mice, the labyrinth is with 75% alcohol wipe and dry.
3. experimental result
All experimental datas are all used means standard deviation, and (x ± s) expression adopts SPSS18.0 software to carry out statistical analysis, and average relatively adopts two tail t checks between two groups, uses variance analysis, reuse LSD statistical analysis when difference has significance relatively earlier between many groups.P＜0.05 is for there being significant difference.
Table 1 Riboflavin Tetrabutyrate is to the influence of the overhead cross of mice labyrinth behavior
| Group | n | Dosage (mg/kg) | Open arm and enter number of times percentage ratio (%) | Open arm holdup time percentage ratio (%) |
| The blank group | 15 | — | 34.4±17.2 | 34.7±18.9 |
| Stable group | 15 | 2 | 50.5±15.8﹡﹡ | 59.1±20.6﹡﹡ |
| The buspirone group | 15 | 5 | 48.0±19.9﹡ | 49.4±22.2﹡ |
| RTB 20mg/kg group | 15 | 20 | 46.7±16.1﹡ | 49.6±17.5﹡ |
| RTB 40mg/kg group | 15 | 40 | 49.6±16.4﹡ | 50.1±18.5﹡ |
| RTB 80mg/kg group | 15 | 80 | 42.2±12.8 | 41.0±11.5 |
Compare ， ﹡ p＜0.05 ， ﹡ ﹡ p＜0.01 with the blank group
Elevated plus-maze test is classical anxiety experimental animal model.More be ready to rest on for the animal of anxiolytic drugs to close arm and avoid out arm.Effectively anxiolytic drugs is not changing under the mobility condition of mice, and the number of times percentage ratio and the holdup time percentage ratio that cause mice to enter out arm increase.Riboflavin Tetrabutyrate low dosage and middle dosage have increased and open arm and enter number of times percentage ratio and open arm holdup time percentage ratio in this experiment, show that this medicine has effect antianxity.
Embodiment 2: mice novel foodstuff consumption experiment
1. grouping and administration
Laboratory animal is a SPF level male mice in kunming, and body weight 20-22g raises in 12/12 hour light and shade circulation environment, and 22 ± 2 ° of C of temperature do not limit drinking water to raise three days.Fasting is 16 hours before the experiment, and grouping and administration situation are with embodiment 1 in detail.
2. experimental technique
Behind every treated animal administration 60min, every mice is placed a dried and clean plastic casing (24cm * 10cm * 8cm).Same position is put into the surface plate of a diameter 9cm in each box, and the quantitative novel foodstuff of interior Sheng (Mus material powder: salad oil=2:1).Write down the food consumption quantity in every mice 5min, calculate the amount that the every g body weight of mice consumes food, represent with mg/g.
3. experimental result
All (x ± s) expression adopts SPSS18.0 software to carry out statistical analysis to all experimental results, and average relatively adopts two tail t checks between two groups, uses variance analysis, reuse LSD statistical analysis when difference has significance relatively earlier between many groups with means standard deviation.P＜0.05 is for there being significant difference.
The influence that table 2 Riboflavin Tetrabutyrate consumes the mice novel foodstuff
| Group | n | Dosage (mg/kg) | Every g body weight consumes quantity of food (mg/g) |
| The blank group | 15 | — | 6.78±2.7 |
| The diazepam group | 15 | 2 | 10.4±4.3﹡﹡ |
| The buspirone group | 15 | 5 | 8.55±2.89 |
| RTB 20mg/kg group | 15 | 20 | 8.2±4.4 |
| RTB 40mg/kg group | 15 | 40 | 10.2±2.9﹡ |
| RTB 80mg/kg group | 15 | 80 | 9.9±4.1 ﹡ |
Compare ， ﹡ p＜0.05 ， ﹡ ﹡ p＜0.01 with the blank group
Mice can be suppressed the irritant reaction of novel foodstuff in novel environment, also can reduce the consumption of food, and the anxiolytic drugs this trophic behavior that can overturn reduces the incubation period that novel foodstuff is consumed and increases consumption to novel foodstuff.Compare with the blank group, the middle and high dosage of Riboflavin Tetrabutyrate has increased the consumption of mouse unit body weight to novel foodstuff respectively, has shown the angst resistance effect of this medicine.
Embodiment 3: the experiment of mice autonomic activities
1. grouping and administration
Laboratory animal is a SPF level male mice in kunming, and body weight 20-22g raises in 12/12 hour light and shade circulation environment, and 22 ± 2 ° of C of temperature do not limit drinking water to raise three days.Be divided into 4 groups at random, i.e. blank group (0.5% carboxymethylcellulose sodium solution), RTB low (20mg/kg), in (40mg/kg), high (80mg/kg) dosage group, gastric infusion, administration volume 10ml/kg.
2. experimental technique
The general behavior of observed and recorded mice before the administration, pupil, posture, gait, have or not situations such as sialorrhea, amyostasia, and mice put into its movable number of times at 5min of autonomic activities case record, use with quadrat method measure after the administration 30,60,90,120, the autonomic activities number of times of 180min.When autonomic activities is measured before the administration, earlier mice is put into the autonomic activities case and be familiar with environment 5min, observe 5min then, be the autonomic activities number of times of this time point.
3. experimental result
All (x ± s) expression adopts SPSS18.0 software to carry out statistical analysis to all experimental results, and average relatively adopts two tail t checks between two groups, uses variance analysis, reuse LSD statistical analysis when difference has significance relatively earlier between many groups with means standard deviation.P＜0.05 is for there being significant difference.
Table 3 Riboflavin Tetrabutyrate is to the influence of mice autonomic activities
| Grouping | Blank group | RTB | RTB | RTB |
| Dosage (mg/kg) | — | 20 | 40 | 80 |
| 0min takes medicine | 42.2±21.2 | 55.0±22.8 | 59.0±32.5 | 61.5±32.2 |
| 30min takes medicine | 39.4±21.6 | 42.5±19.2 | 52.0±22.5 | 36.5±26.9 |
| 60min takes medicine | 53.0±25.5 | 43.0±19.7 | 54.7±27.8 | 56.9±29.0 |
| 90min takes medicine | 41.8±26.6 | 32.0±17.4 | 39.0±24.3 | 52.0±24.4 |
| 120min takes medicine | 49.9±25.0 | 44.0±17.4 | 49.5±26.1 | 60.9±26.5 |
| 180min takes medicine | 40.2±25.8 | 21.9±13.7 | 28.5±22.4 | 42.0±29.4 |
Compare ， ﹡ p＜0.05 ， ﹡ ﹡ p＜0.01 with the blank group, n=12
The result shows that general behavior, pupil, posture, the gait of respectively organizing mice after the administration are all normal, sialorrhea, amyostasia phenomenon do not occur, and response situation is similar to the blank group.
Data show in the table 3, mice does not more all have significant difference at the movable number of times and the matched group of each time point after the administration.The activeness not influence of this medicine to mice is described, no central nervous system's sedation.
Above-mentioned pharmacological evaluation shows that medicine of the present invention has effect antianxity and effect trend, and does not have sedative activity, can be applied to the preparation of angst resistance effect medicine, has the value of actual popularization.
Claims (3)
1. the application of Riboflavin Tetrabutyrate in the preparation anxiolytic drugs is characterized in that: the pharmaceutical preparation that Riboflavin Tetrabutyrate is used to prepare treatment and prevention of anxiety.
2. the application of Riboflavin Tetrabutyrate according to claim 1 in the preparation anxiolytic drugs, it is characterized in that: Riboflavin Tetrabutyrate and various medicinal ingredient or pharmaceutical carrier are formed pharmaceutical composition or complex.
3. the application of Riboflavin Tetrabutyrate according to claim 1 and 2 in the preparation anxiolytic drugs, it is characterized in that: Riboflavin Tetrabutyrate directly uses separately, or form compound recipe with other medicines and use, or use different pharmaceutic adjuvants, make solid preparation or liquid preparation.
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| CN 201110148367 CN102266342B (en) | 2011-06-03 | 2011-06-03 | Application of riboflavin tetrabutyrate to preparation of anxiolytic medicament |
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| CN102266342A true CN102266342A (en) | 2011-12-07 |
| CN102266342B CN102266342B (en) | 2013-08-14 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007144676A2 (en) * | 2006-06-13 | 2007-12-21 | Freund Tamas | Use of echinacea or preparations thereof in compositions for the treatment of anxiety |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007144676A2 (en) * | 2006-06-13 | 2007-12-21 | Freund Tamas | Use of echinacea or preparations thereof in compositions for the treatment of anxiety |
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